Egg freezing (fertility preservation)

The egg is the largest cell in the body and is contained mostly of water. The classic problem with freezing eggs has been that as the temperature drops below freezing point, ice crystals form inside the egg and cause damage to the genetic material. Vitrification is an ultra rapid cooling technique that allows the water inside and surrounding the egg to instantaneously super cool into a solid state with no ice crystal formation at all.

In Japan, where vitrification techniques were developed, scientists have shown that 90%-95% of eggs can survive the new freezing method compared with 50%-60% using conventional methods. Vitrification has shown pregnancy rates of 30%-40%, which is comparable to the use of fresh eggs.

The technique involves removing water from the eggs then freezing them at high speed in liquid nitrogen to prevent any damaging crystals from forming. Studies have shown that vitrification results in higher post-warming survival, fertilisation, embryo development and pregnancy rates.

There are many situations when it may be suitable to store eggs, these may include:

when a younger woman wants to preserve her fertility and store eggs while she is still young;

when a single woman is at risk of losing her fertility as a result of chemotherapy or other cytotoxic therapy; or

if ethical/religious considerations do not permit the storage of embryos.

Egg vitrification at CRGW

Egg vitrification is currently offered for use at CRGW for patients with medical reasons (eg: prior to chemotherapy, Turners Syndrome) or in cases of emergency (eg: no sperm available on the day of egg collection). CRGW also offers egg vitrification for social reasons.
Our lead embryologist, Lyndon Miles has been vitrifying embryos clinically since 2006 which resulted in an immediate increase in thaw survival and pregnancy rates from frozen embryo transfer. Lyndon’s work resulted in the first vitrification baby born in Wales. Since then, many babies have been born in Wales and across the UK with vitrified embryos.

Success rates using vitrified eggs

A recent clinical study carried out in of 57 volunteers* (693 vitrified eggs) found the following:

96.1% vitrified eggs survived the warming procedure

73.1% of warmed eggs were fertilised

38.5% implantation rate per embryo

63.2% pregnancy rate per transfer

A recent review of obstetric and perinatal outcomes in 200 infants conceived following egg vitrification cycles**, found no increased incidents of anomalies when compared to infants conceived naturally or through IVF. These studies provide reassuring evidence that vitrification preserves the biological integrity of eggs, resulting in high survival and pregnancy rates.

A woman’s natural fertility is highest in her late teens and twenties. Although a woman will ovulate every month almost until the age of 50, her actual fertility (chance of getting pregnant) declines significantly from her early thirties. Of course individuals vary enormously, and lifestyle factors like smoking and increased body weight play an important (negative) role too.

The reduction in fertility is not only due to the decline in the number of eggs left in the ovary over time, but it is also related to an increase in the proportion of abnormal eggs. This leads to both a lower chance of conception and also an increased risk of miscarriage.

The indication that the problem lies with using ‘older’ eggs can be deduced from the interesting scientific model seen when older women receive eggs donated from a younger woman.

Table 1 below, shows that women in their 40s perform poorly in an IVF programme with pregnancy rates, <10% per cycle. However, when they are provided with donor eggs from younger women, they can achieve pregnancy rates nearer to 50% per cycle, which results in live birth rates in excess of 35% per cycle throughout the age range.

Table 1. Live birth rate per IVF cycle (HFEA current data)

Age (years)

<35

35-37

38-39

40-42

43-44

Live birth rate (%)

32.1

27.2

20.6

13.2

5.8

In developed and developing countries there is now a steady shift towards having babies later in life and it is expected that it will become common practice to freeze eggs as an insurance measure.

Fertility Preservation

In the past, individuals could only freeze embryos (eggs already fertilised with sperm), which of course required a stable heterosexual relationship. The embryo is a collection of small cells which survive the freezing process quite well. On the other hand, the mature human egg is a large cell with a complex internal structure which is often irreparably damaged by conventional freezing methods.

Recently, methods have been developed that allow safer freezing of mature eggs which survive freezing and thawing and lead to successful pregnancies at a rate similar to frozen embryos. These methods have been adopted in some centres over the last few years and the results are encouraging.

Although only a few hundred babies have been born worldwide so far, the reports are satisfactory and reliable.

Egg Vitrification

The latest breakthrough on this technology is the use of a process for storage called vitrification. It works by removing nearly all the water from the egg cell by osmosis.

The egg can then be stored at the same low temperatures as frozen eggs without damage. Published results indicate that there is negligible damage to the egg caused by these procedures, resulting in success rates, after fertilization, which are identical to fresh eggs.At CRMW we use this method as the preferred means of storage.

It is important to realise that the decline in fertility is due to the “age of the eggs” and therefore fertility preservation should apply only to women who are less than 36 years of age. There are exceptional circumstances (e.g. a higher than average level of AMH) when it may be a viable option up to the age of 38 years.

What is involved?

The procedures for putting your fertility on ice are very similar to a standard IVF cycle. It involves a course of daily fertility drug injections for approximately two weeks followed by an operation to remove the eggs. The eggs are then carefully vitrified and put into store in liquid nitrogen at -196 degrees C. They can be kept under these conditions without deteriorating for an indeterminate length of time.

When you decide that it is time to use these eggs, they will be thawed at the appropriate time of your menstrual cycle, fertilized using ICSI (intracytoplasmic sperm injection) the injection of a single sperm into the egg, and transferred to your womb a couple of days later.

Objective statistics and expectations, using vitrification

These simple statistics are based on a single treatment cycle yielding enough eggs to provide a reasonable chance of success. If you respond to treatment by obtaining 10 eggs, we would expect that on average, eight of these will be mature and suitable for freezing. We would anticipate that all of these would survive the freezing and thawing processes successfully. Upon thawing, the eggs are subjected to ICSI and fertilization would be confirmed the next day. We can estimate that this would yield approximately six viable embryos.

On average, depending upon age at freezing, each embryo trasnfer has an approximately 30% chance of leading to a live birth. Of course there will be wide individual variation around each of those figures, but they do indicate the potential success of the treatment. Younger women would expect to produce more than 10 eggs, each of which would have a higher expectation of implantation than older women. Hence, the younger the woman at the stage of treatment – the better results can be expected.

The age of the woman at the stage of thawing and implantation has a negligible impact upon outcome.

WHAT IS INVOLVED IN THE TREATMENT FOR EGG VITRIFICATION?

Prior to undergoing the procedure, we would assess your ability to respond to the fertility drugs (ovarian assessment), as a small number of individuals, although normally fertile, do not respond with sufficient eggs in any one cycle. As can be seen from Table 1, the earlier you decide to undertake the procedure the better chances of success.

After you make the decision to proceed, a few tests are required, for different reasons and you will also have to provide your consent to undergo the treatment.

Assessments and Tests

Rubella - German measles (blood sample)

Hepatitis B & C

HIV

Test 2 and 3 are required by all cases of gamete or embryo storage to ensure that only virus free tissues are stored in the same container.

THE TREATMENT CYCLE - CONTROLLED OVARIAN STIMULATION

A high egg yield is normally required to maximise the potential of any treatment cycle. This is normally attained by using a procedure called “controlled ovarian stimulation with the GnRH-agonist”.

In some cases we may recommend the use of an alternative approach using a GnRH-antagonist.

Controlled Ovarian Stimulation with GnRH-Agonist
Stage 1

GnRH-agonists are used to prevent premature ovulation – this down-regulation injection is given around day 21 of a menstrual cycle.

In the protocol using the GnRH-Antagonist the “down-regulation” is introduced after starting the FSH injections.

Following your period you will have a blood test and a scan prior to starting your daily injections of follicle stimulating hormone (FSH)

You will be taught how to give these injections.

We monitor your response to the injections by taking blood samples and transvaginal ultrasound scans.

The average number of days to be on injections is 10-12 days.

Once the monitoring indicates that an adequate number of maturing follicles are present, a final hormone injection, the HCG, will be given to complete the maturation process. The timing of this HCG injection is critical and it must be given at the time specified by the team at CRMW. It is also self-administered.

Stage 2

On the day arranged, report to CRMW at the appointed time. You are required to fast before the procedure, as sedation is used.

Do not eat or drink anything after 12 midnight on the day of egg collection, although you may have a glass of water two hours prior to admission.

Sedation

For your comfort this procedure is performed under sedation. The doctor will discuss the procedure with you. An intravenous cannula (venflon) will be placed in your hand, through which your sedation will be given. You will feel yourself drifting off to sleep, although you may still be aware of noise and touch.

Procedure

The stimulated ovaries are visualised on the ultrasound monitor. A fine needle is passed down a specialised guide attached to the ultrasound probe. The needle is directed into the centre of each follicle (the structure containing the egg) and suction is applied to aspirate the contents of the follicle. The fluid is examined by the embryologist to look for the egg. The follicle is washed out with special flushing medium which is also checked. The procedure is finished when all the follicles have been aspirated. The procedure takes about 20-30 minutes.

You will be transferred to the recovery room and allowed to rest until you feel ready to go home, usually 1-2 hours.

You will need to be collected by a responsible adult as you are not allowed to drive for the next 24 hours, as the effects of sedation will still be in your system.

If you feel that egg (oocyte) freezing might be for you, and would like to learn more about your options, we would be pleased to see you.